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Disulfiram treats peritoneal and gouty inflammation via targeting NLRP3 inflammasome activation

Disulfiram treats peritoneal and gouty inflammation via targeting NLRP3 inflammasome activation Disulfiram treats peritoneal and gouty inflammation via targeting NLRP3 inflammasome activation
Disulfiram treats peritoneal and gouty inflammation via targeting NLRP3 inflammasome activation Disulfiram treats peritoneal and gouty inflammation via targeting NLRP3 inflammasome activation

What's new?

In peritoneal and gouty inflammation patients, clinicians may use DSF (disulfiram) to minimize the severity of disease progression.

A recent study identified that treatment with DSF (an old alcohol aversion drug) shows substantial
therapeutic effects on the peritoneal and gouty inflammation. This drug could effectively inhibit NLRP3 (NOD-, LRR- and pyrin domain-containing protein) inflammasome activation and suppress pyroptotic cell death.

Mediation of your innate immune system involves an essential role of NLRP3 inflammasome. Its aberrant activation may contribute to the progression of numerous deleterious disorders like acute liver injury, sepsis, acute peritonitis, gout, and others.

Moreover, in the clinics, there is a paucity of medications targeting NLRP3 inflammasome. For clinical trials, reutilizing marketed drugs, which have shown good safety and pharmacokinetic profiles was a strategy in order to develop novel NLRP3 inflammasome inhibitors.

The findings of the study revealed a direct inhibitory effect of DSF on NLRP3 inflammasome activation. DSF prevented the release of lysosomal cathepsin B into the cytoplasm. This, in turn, hampered NLRP3 inflammasome activation. DSF also diminished mitochondrial-independent ROS (reactive oxygen species) production.

In LPS (lipopolysaccharide)-induced peritoneal inflammation and MSU (monosodium urate crystals)-induced gouty inflammation, administration of DSF thus showed substantial therapeutic effects. This study yielded a potential pharmacological approach to treat NLRP3-driven diseases and a tool to study NLRP3 biology.

Source:

ScienceDirect

Article:

Disulfiram suppresses NLRP3 inflammasome activation to treat peritoneal and gouty inflammation

Authors:

Wenmin Deng et al.

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